title: Severe obesity and diabetes insipidus in a patient with PCSK1 deficiency.
abstract: Non-synonymous mutations affecting both alleles of PCSK1 (proprotein convertase 1/3) are associated with obesity and impaired prohormone processing. We report a proband who was compound heterozygous for a maternally inherited frameshift mutation and a paternally inherited 474kb deletion that encompasses PCSK1, representing a novel genetic mechanism underlying this phenotype. Although pro-vasopressin is not a known physiological substrate of PCSK1, the development of central diabetes insipidus in this proband suggests that PCSK1 deficiency can be associated with impaired osmoregulation.
authors.affiliation: Cohen Children's Medical Center, Division of Pediatric Endocrinology, New Hyde Park, NY 11042, USA.
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Frank
authors.forename: Joyce
authors.initials: J
authors.lastname: Fox
authors.forename: Ninfa
authors.initials: N
authors.lastname: Candela
authors.forename: Zorica
authors.initials: Z
authors.lastname: Jovanovic
authors.forename: Elena
authors.initials: E
authors.lastname: Bochukova
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Levine
authors.forename: Peter R
authors.initials: PR
authors.lastname: Papenhausen
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Rahilly
authors.forename: I Sadaf
authors.initials: IS
authors.lastname: Farooqi
mesh_terms: D000483:Alleles; D002675:Child, Preschool; D003919:Diabetes Insipidus / Q000150:complications / Q000235:genetics* / Q000473:pathology; D004700:Endocrine System Diseases / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D007223:Infant; D009154:Mutation; D009765:Obesity / Q000150:complications / Q000235:genetics* / Q000473:pathology; D009767:Obesity, Morbid / Q000150:complications / Q000235:genetics* / Q000473:pathology; D064587:Osmoregulation / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D045664:Proprotein Convertase 1 / Q000172:deficiency* / Q000235:genetics; D043484:Proprotein Convertases / Q000235:genetics*
chemical_list: D043484:Proprotein Convertases; D045664:Proprotein Convertase 1
keywords: Obesity; Prohormones